Page 135 - The clinical aspects and management of chronic migraine Judith Anne Pijpers

of migraine-specific acute medication is associated with persistent alterations in dural afferents in animal studies.32 The evident peripheral effect of medication overuse on the trigeminovascular system might explain that medication overuse is a more prominent risk factor for migraine chronification as opposed to pain chronification in general.
Chronic migraine and affective disorders
This thesis also stresses the association between affective disorders, migraine chronification and central sensitization processes. Depression is a known major risk factor for migraine chronification,33,34 which was confirmed in chapter 2 by showing that both depression-specific and general symptom dimensions of affective disorders are associated with both high attack frequency and cutaneous allodynia. Moreover, this association was strongest for somatic arousal, anxiety specific symptoms. Recently,kappaopioidreceptors(KOR)andtheirliganddynorphinintheamygdala have been related to central sensitisation in animal models of medication overuse. Allodynia and lack of pain inhibition after triptan or morphine sensitisation, were reverted by blockage of KOR in the amygdala.30,35,36 The dynorphin-KOR pathway in the amygdala is also described in the pathophysiology of anxiety: KOR agonists induce anxiety, whereas KOR antagonists diminish anxiety. Similar relations have been identified with depressive behaviour and substance dependency.37 Therefore the dynophin-KOR pathway could (partly) explain the close relationship between frequent medication use, anxiety, depression and allodynia as risk factors for migraine chronification.
Future research perspectives
The pathways associated with migraine chronification, including trigeminovascular activation, central sensitization by enhanced pain facilitation of the ascending pain pathway and lack of pain inhibition by the descending pain pathway, are described as separate processes, but in reality these mechanism are closely related and co-dependent. Therefore, to understand pathophysiology, a combination of multiple read-outs in episodic and chronic migraine patients would be necessary. Although time consuming, long term follow-up studies in (low frequent) episodic migraine patients with elaborate baseline measurements, would be highly advantageous to specify characteristics of
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Summary and general discussion
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